title: Evolution and dynamics of regulatory architectures controlling polymyxin B resistance in enteric bacteria.
abstract: Complex genetic networks consist of structural modules that determine the levels and timing of a cellular response. While the functional properties of the regulatory architectures that make up these modules have been extensively studied, the evolutionary history of regulatory architectures has remained largely unexplored. Here, we investigate the transition between direct and indirect regulatory pathways governing inducible resistance to the antibiotic polymyxin B in enteric bacteria. We identify a novel regulatory architecture -- designated feedforward connector loop -- that relies on a regulatory protein that connects signal transduction systems post-translationally, allowing one system to respond to a signal activating another system. The feedforward connector loop is characterized by rapid activation, slow deactivation, and elevated mRNA expression levels in comparison with the direct regulation circuit. Our results suggest that, both functionally and evolutionarily, the feedforward connector loop is the transitional stage between direct transcriptional control and indirect regulation.
authors.affiliation: Howard Hughes Medical Institute, Washington University, St Louis, MO, USA.
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Mitrophanov
authors.forename: Mollie W
authors.initials: MW
authors.lastname: Jewett
authors.forename: Tricia J
authors.initials: TJ
authors.lastname: Hadley
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Groisman
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D024881:Drug Resistance, Bacterial; D004755:Enterobacteriaceae / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D010802:Phylogeny; D011112:Polymyxin B / Q000494:pharmacology*; D014158:Transcription, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011112:Polymyxin B